Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma: Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
30
09
2022
accepted:
28
12
2022
medline:
15
5
2023
pubmed:
16
2
2023
entrez:
15
2
2023
Statut:
ppublish
Résumé
The aim of this study was to evaluate the clinical implications of the proximal bile duct margin status in resection of perihilar cholangiocarcinoma (PHCC). Intraoperative frozen section (IFS) analysis to assess the bile duct margin status is commonly used during PHCC resection. However, the impact of additional resection after obtaining a positive margin on the long-term outcome remains unclear. Among the 257 patients who underwent PHCC resection, 190 patients with a negative distal margin were included and analyzed. IFS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of either invasive cancer, or carcinoma, in situ. IFS analysis revealed an initial positive margin in 69 (36%) patients. Among 20 patients who underwent re-resection, only 11 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes: recurrence-free survival (RFS) and overall survival (OS) were 16 and 25 months for patients with an initial positive margin, but 47 and 63 months for patients with an initial negative margin, respectively (p < 0.0001). In contrast, there was no difference in RFS or OS between patients with a secondary R0 margin, and those with a final R1 margin (14 vs. 16 months for RFS, p = 0.98, and 23 versus 25 months for OS, p = 0.63, respectively). An IFS-positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable PHCC. Additional resection has minimal impact on survival, even when negative margin is achieved.
Sections du résumé
BACKGROUND
BACKGROUND
The aim of this study was to evaluate the clinical implications of the proximal bile duct margin status in resection of perihilar cholangiocarcinoma (PHCC). Intraoperative frozen section (IFS) analysis to assess the bile duct margin status is commonly used during PHCC resection. However, the impact of additional resection after obtaining a positive margin on the long-term outcome remains unclear.
PATIENTS AND METHODS
METHODS
Among the 257 patients who underwent PHCC resection, 190 patients with a negative distal margin were included and analyzed. IFS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of either invasive cancer, or carcinoma, in situ.
RESULTS
RESULTS
IFS analysis revealed an initial positive margin in 69 (36%) patients. Among 20 patients who underwent re-resection, only 11 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes: recurrence-free survival (RFS) and overall survival (OS) were 16 and 25 months for patients with an initial positive margin, but 47 and 63 months for patients with an initial negative margin, respectively (p < 0.0001). In contrast, there was no difference in RFS or OS between patients with a secondary R0 margin, and those with a final R1 margin (14 vs. 16 months for RFS, p = 0.98, and 23 versus 25 months for OS, p = 0.63, respectively).
CONCLUSION
CONCLUSIONS
An IFS-positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable PHCC. Additional resection has minimal impact on survival, even when negative margin is achieved.
Identifiants
pubmed: 36790733
doi: 10.1245/s10434-023-13190-3
pii: 10.1245/s10434-023-13190-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3348-3359Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. Society of Surgical Oncology.
Références
Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nimura Y. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258(1):129–40.
doi: 10.1097/SLA.0b013e3182708b57
pubmed: 23059502
Kosuge T, Yamamoto J, Shimada K, Yamasaki S, Makuuchi M. Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection. Ann Surg. 1999;230(5):663–71.
doi: 10.1097/00000658-199911000-00008
pubmed: 10561090
pmcid: 1420920
Matsuo K, Rocha FG, Ito K, D’Angelica MI, Allen PJ, Fong Y, Dematteo RP, Gonen M, Endo I, Jarnagin WR. The Blumgart preoperative staging system for hilar cholangiocarcinoma: analysis of resectability and outcomes in 380 patients. J Am Coll Surg. 2012;215(3):343–55.
doi: 10.1016/j.jamcollsurg.2012.05.025
pubmed: 22749003
Natsume S, Ebata T, Yokoyama Y, Igami T, Sugawara G, Shimoyama Y, Nagino M. Clinical significance of left trisectionectomy for perihilar cholangiocarcinoma: an appraisal and comparison with left hepatectomy. Ann Surg. 2012;255(4):754–62.
doi: 10.1097/SLA.0b013e31824a8d82
pubmed: 22367444
Matsumoto N, Ebata T, Yokoyama Y, Igami T, Sugawara G, Shimoyama Y, Nagino M. Role of anatomical right hepatic trisectionectomy for perihilar cholangiocarcinoma. Br J Surg. 2014;101(3):261–8.
doi: 10.1002/bjs.9383
pubmed: 24399779
Sakamoto E, Nimura Y, Hayakawa N, Kamiya J, Kondo S, Nagino M, Kanai M, Miyachi M, Uesaka K. The pattern of infiltration at the proximal border of hilar bile duct carcinoma: a histologic analysis of 62 resected cases. Ann Surg. 1998;227(3):405–11.
doi: 10.1097/00000658-199803000-00013
pubmed: 9527064
pmcid: 1191279
Ebata T, Watanabe H, Ajioka Y, Oda K, Nimura Y. Pathological appraisal of lines of resection for bile duct carcinoma. Br J Surg. 2002;89(10):1260–7.
doi: 10.1046/j.1365-2168.2002.02211.x
pubmed: 12296893
Konishi M, Iwasaki M, Ochiai A, Hasebe T, Ojima H, Yanagisawa A. Clinical impact of intraoperative histological examination of the ductal resection margin in extrahepatic cholangiocarcinoma. Br J Surg. 2010;97(9):1363–8.
doi: 10.1002/bjs.7122
pubmed: 20632323
Oguro S, Esaki M, Kishi Y, Nara S, Shimada K, Ojima H, Kosuge T. Optimal indications for additional resection of the invasive cancer-positive proximal bile duct margin in cases of advanced perihilar cholangiocarcinoma. Ann Surg Oncol. 2015;22(6):1915–24.
doi: 10.1245/s10434-014-4232-2
pubmed: 25404474
Ribero D, Amisano M, Lo Tesoriere R, Rosso S, Ferrero A, Capussotti L. Additional resection of an intraoperative margin-positive proximal bile duct improves survival in patients with hilar cholangiocarcinoma. Ann Surg. 2011; 254(5):776-81; discussion 781-3.
Takahashi Y, Ito H, Inoue Y, Mise Y, Ono Y, Sato T, Saiura A. Preoperative biliary drainage for patients with perihilar bile duct malignancy. J Gastrointest Surg. 2019;24(7):1630–8.
doi: 10.1007/s11605-019-04231-y
pubmed: 31197684
Takahashi Y, Sasaki T, Sasahira N, Ito H, Ishizuka N, Inoue Y, Mise Y, Sato T, Ono Y, Oba A, Saiura A. Safety and efficacy of inside-stent as bridging therapy for malignant hilar biliary obstruction: single-centre prospective study. Br J Surg. 2022;109(5):468–9.
doi: 10.1093/bjs/znac009
pubmed: 35174384
Nagino M, DeMatteo R, Lang H, Cherqui D, Malago M, Kawakatsu S, DeOliveira ML, Adam R, Aldrighetti L, Boudjema K, Chapman W, Clary B, de Santibañes E, Dong J, Ebata T, Endo I, Geller D, Guglielmi A, Kato T, Lee SG, Lodge P, Nadalin S, Pinna A, Polak W, Soubrane O, Clavien PA. Proposal of a new comprehensive notation for hepatectomy: the “new world” terminology. Ann Surg. 2021;274(1):1–3.
doi: 10.1097/SLA.0000000000004808
pubmed: 33630445
TNM Classification of Malignant Tumours. 8th edn. Hoboken: Wiley, 2017
Endo I, House MG, Klimstra DS, Gönen M, D’Angelica M, Dematteo RP, Fong Y, Blumgart LH, Jarnagin WR. Clinical significance of intraoperative bile duct margin assessment for hilar cholangiocarcinoma. Ann Surg Oncol. 2008;15(8):2104–12.
doi: 10.1245/s10434-008-0003-2
pubmed: 18543039
Ruys AT, van Beem BE, Engelbrecht MR, Bipat S, Stoker J, Van Gulik TM. Radiological staging in patients with hilar cholangiocarcinoma: a systematic review and meta-analysis. Br J Radiol. 2012;85(1017):1255–62.
doi: 10.1259/bjr/88405305
pubmed: 22919007
pmcid: 3487057
Hirose T, Igami T, Ebata T, Yokoyama Y, Sugawara G, Mizuno T, Mori K, Ando M, Nagino M. Surgical and radiological studies on the length of the hepatic ducts. World J Surg. 2015;39(12):2983–9.
doi: 10.1007/s00268-015-3201-7
pubmed: 26296838
Nishio H, Hidalgo E, Hamady ZZ, Ravindra KV, Kotru A, Dasgupta D, Al-Mukhtar A, Prasad KR, Toogood GJ, Lodge JP. Left hepatic trisectionectomy for hepatobiliary malignancy: results and an appraisal of its current role. Ann Surg. 2005;242(2):267–75.
doi: 10.1097/01.sla.0000171304.70678.11
pubmed: 16041218
pmcid: 1357733
Halazun KJ, Al-Mukhtar A, Aldouri A, Malik HZ, Attia MS, Prasad KR, Toogood GJ, Lodge JP. Right hepatic trisectionectomy for hepatobiliary diseases: results and an appraisal of its current role. Ann Surg. 2007;246(6):1065–74.
doi: 10.1097/SLA.0b013e3181492795
pubmed: 18043112
Mantel HT, Westerkamp AC, Sieders E, Peeters PM, de Jong KP, Boer MT, de Kleine RH, Gouw AS, Porte RJ. Intraoperative frozen section analysis of the proximal bile ducts in hilar cholangiocarcinoma is of limited value. Cancer Med. 2016;5(7):1373–80.
doi: 10.1002/cam4.693
pubmed: 27062713
pmcid: 4944862
Zhang XF, Squires MH 3rd, Bagante F, Ethun CG, Salem A, Weber SM, Tran T, Poultsides G, Son AY, Hatzaras I, Jin L, Fields RC, Weiss M, Scoggins C, Martin RCG, Isom CA, Idrees K, Mogal HD, Shen P, Maithel SK, Schmidt CR, Pawlik TM. The impact of intraoperative re-resection of a positive bile duct margin on clinical outcomes for hilar cholangiocarcinoma. Ann Surg Oncol. 2018;25(5):1140–9.
doi: 10.1245/s10434-018-6382-0
pubmed: 29470820
Ma WJ, Wu ZR, Shrestha A, Yang Q, Hu HJ, Wang JK, Liu F, Zhou RX, Li QS, Li FY. Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma. Hepatobiliary Surg Nutr. 2018;7(4):251–69.
doi: 10.21037/hbsn.2018.03.14
pubmed: 30221153
pmcid: 6131255
Otsuka S, Ebata T, Yokoyama Y, Mizuno T, Tsukahara T, Shimoyama Y, Ando M, Nagino M. Clinical value of additional resection of a margin-positive distal bile duct in perihilar cholangiocarcinoma. Br J Surg. 2019;106(6):774–82.
doi: 10.1002/bjs.11125
pubmed: 30889275
Shingu Y, Ebata T, Nishio H, Igami T, Shimoyama Y, Nagino M. Clinical value of additional resection of a margin-positive proximal bile duct in hilar cholangiocarcinoma. Surgery. 2010;147(1):49–56.
doi: 10.1016/j.surg.2009.06.030
pubmed: 19767048
Ikeda M, Nakachi K, Konishi M, Nomura S, Katayama H, Kataoka T, Uesaka K, Yanagimoto H, Morinaga S, Wada H, Shimada K, Takahashi Y, Nakagohri T, Gotoh K, Kamata K, Shimizu Y, Ueno M, Ishii H, Okusaka T, Furuse J. Adjuvant S-1 versus observation in curatively resected biliary tract cancer: a phase III trial (JCOG1202: ASCOT). J Clin Oncol. 2022;40(4_suppl):382–382.
doi: 10.1200/JCO.2022.40.4_suppl.382
Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663–73.
doi: 10.1016/S1470-2045(18)30915-X
pubmed: 30922733